This project will define the relationship between intracellular invasion and group A streptococcal pathogenesis. Experiments will further investigate the molecular mechanisms by which streptococci commandeer the extracellular matrix (ECM) and receptor signaling systems of host cells to reach an intracellular state. In vivo experiments will investigate the role of intracellular invasion in persistent infection of nasal associated lymphoid tissue, employing a murine intranasal infection model. Experiments will evaluate whether streptococci preferentially infect this tissue. We propose that persistence depends on the potential of streptococci to be efficiently ingested by specific cells in this lymphoid tissue. Information gained from this study may identify new targets for antibiotic development, and increase our understanding of the mechanisms by which this pathogen persists in human populations.